The overall goal of the Protein Identification Core of the UIUC Neuroproteomics Center on Cell-Cell Signaling is to characterize the protein and peptide complements of a range of samples, with a special emphasis on those involved in intercellular signaling. The intracellular signaling molecules expressed in the cells and tissues under investigation present an extremely complex analytical challenge with a vast number of components, varying dramatically in size and concentration. To address these challenges, and to provide our users with a battery of state-of-the-art protein identification techniques, a range of mass spectrometric approaches are used, including differential gel electrophoresis, mass fingerprinting, tandem sequencing, accurate mass measurements, and top-down intact protein analysis. In addition, spatial localization of intercellular signaling molecules is performed using a variety of mass spectrometric imaging techniques. Our user's needs for intercellular signaling molecule identification and quantitation in the brain are quite different from what is required from proteomics measurements of unicellular organisms and homogenous tissues, particularly with regard to sample size and complexity. Thus, the advanced measurement strategies used in our Center reflect this complexity. With the combined expertise and facilities in the research groups associated with this core, a unique opportunity exists to identify and characterize intercellular signaling peptides and proteins across a surprising range of models and scales.